Anti-influenza hyperimmune immunoglobulin enhances fc-functional antibody immunity during human influenza infection

Hillary A. Vanderven, Kathleen Wragg, Fernanda Ana-Sosa-Batiz, Anne B. Kristensen, Sinthujan Jegaskanda, Adam K. Wheatley, Deborah Wentworth, Bruce D. Wines, P. Mark Hogarth, Steve Rockman, Stephen J. Kent

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Abstract

Background. New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralizing antibody responses to past strains in influenza-infected subjects. The effect of Flu- IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear. Methods. We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fcγ receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study. Results. Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1-3 days against infecting and noninfecting strains of influenza. Conclusions. Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus, and passive transfer of Flu- IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralizing antibodies in the Flu-IVIG preparation.

Original languageEnglish (US)
Pages (from-to)1383-1393
Number of pages11
JournalJournal of Infectious Diseases
Volume218
Issue number9
DOIs
StatePublished - Jan 1 2018

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Keywords

  • ADCC
  • Fc receptor
  • immunoglobulin
  • influenza
  • passive transfer

Cite this

Vanderven, H. A., Wragg, K., Ana-Sosa-Batiz, F., Kristensen, A. B., Jegaskanda, S., Wheatley, A. K., Wentworth, D., Wines, B. D., Hogarth, P. M., Rockman, S., & Kent, S. J. (2018). Anti-influenza hyperimmune immunoglobulin enhances fc-functional antibody immunity during human influenza infection. Journal of Infectious Diseases, 218(9), 1383-1393. https://doi.org/10.1093/infdis/jiy328